Leritrelvir (RAY1216) is an orally active and highly potent protease inhibitor with antiviral activity that blocks cleavage of viral precursor proteins and inhibits viral replication in SARS-CoV-2.

Leritrelvir has a residence time of 104 minutes on the target.
Leritrelvir forms covalent binding to the Cys145 catalytic site via the α-ketoamide warhead.
0-1000 nM Leritrelvir, treated for 72 hours, demonstrated antiviral effects against SARS-CoV-2 wild type and its variants. [1]

Leritrelvir was effective in prolonging the survival time of SARS-CoV-2 infected mice for 5 consecutive days under oral administration conditions in the dose range of 150-600 mg/kg/day. The pharmacokinetic parameters of the drug have been studied in a variety of animals demonstrating the exposure and metabolic properties of the drug.
In mice, the area under the drug curve (AUC(0-last)) at an intravenous (IV) dose of 3.0 mg/kg was 7789 nM/h, but peak concentration (C_max) and time to peak (T_max) were not provided. In comparison, an oral (PO) dose of 10 mg/kg produced a C_max of 1287 nM, a T_max of 2.0 hours, an AUC(0-last) of 5698 nM/h, an elimination half-life (T_1/2) of 2.6 hours, and an oral bioavailability (F%) of 22.
In rats, the intravenous (IV) dose of 2.0 mg/kg yielded an AUC(0-last) of 4505 nM/h, whereas the oral (PO) dose of 10 mg/kg produced a C_max of 916 nM, a T_max of 0.9 h, an AUC(0-last) of 7429 nM/h, a T_1/2 of 4.3 h, and an F% of 33.
In cynomolgus monkeys, the intravenous (IV) dose of 1.0 mg/kg had an AUC(0-last) of 1157 nM/h, whereas the oral (PO) dose of 5.0 mg/kg yielded a C_max of 102 nM, a T_max of 1.5 h, an AUC(0-last) of 458 nM/h, a T_1/2 of 14.9 h, and a F% of 8. [1]